Background: The two pathological hallmarks associated with Alzheimer’s disease (AD) include the accumulation
of senile plaques and the generation of neurofibrillary tangles. Although it is a known fact
that both amyloid beta (Aβ) and Tau exist together in mitochondria, to date, there is no reasonable explanation
for the Aβ and Tau interaction in particular.
Objective: The cross-seeding interactions between Aβ and Tau were studied using the potential of mean
force (PMF) analysis.
Methods: The Aβ- Aβ homo-dimer; Tau-Tau homo-dimer and Aβ-Tau hetero-dimer were constructed
using molecular docking tools. We have used molecular dynamics (MD) simulation with the umbrella
sampling methodology to examine the cross-sequence interactions between homo-dimers and the hetero-
dimer by computing PMF.
Results: We observed the global minimum and energy barrier to be quite higher for both the homodimers
relative to the hetero-dimer, thus indicating that Aβ (25-35) has a high affinity to form dimer
complex with Tau (273-284) monomer. We also observed a relatively higher range of interacting residues
and interface area between the monomeric units in hetero-dimer (Aβ-Tau) the homo-dimer (Aβ-
Aβ) and (Tau-Tau) showed a less number of the same.
Conclusion: From the results we may therefore conclude that Aβ fragments can form complexes with
the Tau monomers which consequently advance to form aggregates. This aggregation may be favored
by interactions between the hydrophobic residues and charged residues present in both the fragments.